Funds are requested for the purchase of an atmospheric pressure ionization (API) tandem quadrupole mass spectrometer (MS/MS) for use in biomedical and other research projects at the University of Minnesota Health Sciences complex. Recent advances in "soft ionization techniques" including the electrospray and ion-spray API methods have made mass spectrometry an extremely important tool in biomedical research. When the ability to produce a molecular ion is coupled with collisionally-induced dissociation (CID), both molecular weight and structural information are available from a single experiment. These capabilities have been well utilized for determination of amino acid sequences of peptides, sequences in oligonucleotides, and structural information about polysaccharides. API methods have been long recognized for their excellent sensitivity, a fact of key importance for producing quantitative data on limited amounts of biological fluids. The proposed research projects make use of the sensitivity of API, the excellent limits of detection of selected reaction monitoring, and the structural elucidation capability of MS/MS as well as the extended mass range (2400 amu) and negative ionization capabilities not available on present Health Sciences instrumentation. The proposed instrument will support a primary users group of seven investigators representing six departments within the Health Sciences. The research projects include linear and cyclic peptide sequencing for immunosuppressive drugs, qualitative and quantitative studies on neurochemically active amino acid analogs and peptides, identification of nucleotide regulatory compounds, quantitative metabolic studies on a nucleotide analog effective against AIDS, and identification of immuno- inhibitory components of mannans from microbes. The requested instrument will join a Hewlett-Packard 5985A GC/MS and a VG Sira II IDMS to provide a Health Sciences Mass Spectrometry Resource. All of the instrumentation in the Resource will be available to any researcher, and operation will be financed by a users fee. The MS/MS will be employed solely for research studies, using soft ionization techniques as well as HPLC/MS/MS and capillary zone electrophoresis/MS/MS. In addition to the primary investigators, faculty utilizing a program project grant laboratory and the molecular biology laboratory will be encouraged to use this instrument. Education of these potential users will be a major goal of the shared facility. The requested instrument will provide the Health Sciences Mass Spectrometry Resource with a state-of-the-art instrument to respond to the diverse requests inherent to such a facility and complement other mass spectrometers available at the University of Minnesota.